Session, w e are glad to have Ms. Jacqueline Shea, CEO, and Mr. Michael Sumner, Chief Medical Officer of INOVIO Pharmaceuticals.
Thank you.
So we know that INOVIO has come a long way to have finally the candidate run. So, to begin with, let's start with the INO-3107 to comment on the mechanism of action and the technology platform it's been on.
Yeah, happy to. So INOVIO, for those of you who don't know INOVIO, INOVIO is a clinical stage biotechnology company that's developing DNA medicines to help treat and prevent HPV-related diseases, cancer, and infectious diseases. Our DNA medicines platform is designed to enable in vivo expression of target proteins within the body's own cells, and this in vivo expression of the target proteins can drive powerful and targeted immune responses. And those immune responses themselves can be part of the mechanism of action, or in the case of DNA-encoded monoclonal antibodies, the protein that we're expressing in vivo can also be the therapeutic product itself. So when we think about RRP, RRP is an HPV-related disease. It's caused by HPV -6 and 11, and it's really a disease where there's a deficiency in the immune response.
Most people can clear HPV -6 and 11 pretty well by themselves, but in people who are suffering from RRP, recurrent respiratory papillomatosis, they get these wart-like growths on the vocal cords that grow back time after time. The mechanism of action, we believe, for INO-3107, is the production of targeted, antigen-specific T -cells with lytic potential, which we believe are able to seek out and destroy these HPV-infected cells and prevent the papillomas from growing back.
Got it. How large is the RRP patient population in the U.S.?
So RRP is a rare disease. We believe that there are about 14,000 patients in the U.S., and there are around three peaks of incidence. So there's a peak at around age seven, and a peak in the thirties, and then a peak in the early sixties.
Do patients currently have any alternative treatment option other than surgery?
No. So in terms of how patients are currently treated, I mean, most patients originally sort of figure out that they have RRP when their voice starts deteriorating, or in the case of children, they may have breathing difficulties. So patients originate pretty quickly. They go to an ENT, they get diagnosed, often referred to a laryngologist, and at the moment, the only potential treatment is repeated surgery time after time.
What clinical data has been generated for INO-3107 so far?
Yeah, I'll hand over to Mike to talk about the clinical data.
Thank you. So we ran a phase I/II study, included 32 patients, and the premise of the study was really to compare the post-treatment number of surgeries compared to the year prior to surgery. An INO-3107 treatment is four injections. So at day zero, they come into the study, having undergone a clinically relevant surgery, start their treatment course, and then following on from that time period, we counted every single surgery, and we did not prescribe any forced laryngoscopy or anything as part of their treatment program. What we actually saw was out of the 32 patients, we saw an 81% response rate, which was basically they had less surgeries in their post-treatment year compared to their prior year. But 28% of those patients actually required no surgery whatsoever during, following their first dose of treatment.
Okay. And this study, study 3107, is qualified for Accelerated Approval pathway, right? What are FDA's requirements for BLA filing?
Yeah. So we were obviously delighted. We received Breakthrough Designation, and then, as part of that process, they actually, we submitted all our phase 1/2 clinical data. And we were granted that. And then following that, the FDA contacted us and said we could use that data to form the clinical aspect of our BLA submission. Obviously, because you get Accelerated Approval, you still have to put in a full CMC package. We still have to put in a full package related to the rest of the combination product. And so we are working to do that, and we're on track to do that in the second half of the year. What they did ask us also to do was to commence our confirmatory study.
We had fortunately been in discussions with the agency around what a phase III study was going to look like. So we'd already engaged with a CRO. We'd already started site identification. So we're now moving forward with the CRO and the clinical trial sites after the FDA confirmed they had no more comments on our confirmatory study design.
I mean, can you comment on the trial design of the confirmatory trial?
Yes.
What aspects of it are different from the completed phase 1/2 trial?
Yeah. So, many aspects remain the same. Obviously, we've kept the treatment regimen. The patients require a surgery to enter into the study. So all those elements are the same, and obviously, we're gonna focus on surgical reduction. But we've decided to run a placebo-controlled study. And the reason we did that was the FDA informed us that if we wanted to utilize the same population in the previous study, which was a minimum number of two surgeries in the prior year, that had to be a placebo-controlled study. If we wanted to just have greater than three surgeries, we would be required to run a prospective arm with no treatment to gather that surgery information and then treat the patients.
So we actually think it's very important to maintain what we've done in the previous study, but also as we think of how the disease is going to be hopefully treated in the future, and we know that these patients get damage to their vocal cords very early on in their surgical history. And so, you know, really being able to start treatment on that second surgery, we think is actually going to be very important. And we've been told by the European regulators that we need to run a placebo-controlled study to get licensure in Europe. And obviously, HPV is a global disease, and so we want to make sure that our clinical package is going to be relevant for all the authorities that we file it in.
If I can just add, in our phase I/II study, we enrolled patients who had had between 2 and 8 surgeries in the prior year. We enrolled patients who had HPV-6 or HPV-11-related disease, also a combination of 6 and 11 in some patients. What we're looking to do in the confirmatory trial is really very much carry on the same patient population that we believe is really representative of the population that needs treatments and is out there.
Got it. Does the FDA stipulate that the confirmatory trial has to be completed within a certain timeframe?
No, they have asked us to commence the study. And, you know, obviously, there's been lots of news articles about people's confirmatory study. You know, certainly in this disease, we believe that the FDA has recognized the immense clinical need, hence they're willing to accept the Accelerated Approval. And, you know, the fact that we in our first trial, we utilized eight clinical trial sites, we're going to expand beyond that. So we think we'll—by the time we're ready to file our BLA, we'll be able to show the FDA that we're really very serious about completing this study in as short a timeframe as possible.
Given the breakthrough device designation, breakthrough designation, therapy designation, should we assume that study 3107 could get expedited when you...?
That is something we will request on our pre-BLA. As I said, I think the FDA recognized the immense clinical need in this population, so I'm hoping they will grant that, but that's only ultimately something that the FDA can.
Is there any special requirement by the FDA running the device you used to deploy study 3107?
So we'll... I mean, obviously there are a lot of requirements around a device, and we are a combination product. We've been fortunate enough to work with this device now from our phase III trials with VGX-3100. So we actually have a lot of experience and a lot of safety data related to that. But as part of our clinical trial, it's a normal device filing. We'll be following all the, you know, design verification, human factors, so a regular, you know, a regular complete device file.
Has the company started preparing for the commercialization of...?
Yeah. So our commercialization plans are well underway, but if I can just comment on the device as well. So our CELLECTRA 5PSP device is a fully integrated device. It delivers the dose and provides the in vivo electroporation with just one press of the button. So it's a very easy-to-use device. Patients have found it very tolerable, and as Mike has said, we've got a large safety database now on using this device across multiple programs. So I think that's really important to bear in mind. So when it comes to commercialization, obviously, we have multiple work streams underway. We're really working to understand both the healthcare provider and the patient landscape.
We've been doing some claims database analysis to really understand where those patients are, which physicians they go to, so that we can really target our field force appropriately. And then we're doing the normal things that you would expect. So we have a temporary CPT code assigned. We're going through the branding and naming process and really thinking about, you know, for a rare disease, how we build up that awareness of a rare disease and that a new therapy is potentially coming to market.
Is there already a reimbursement code that study 3107 can use?
Well, there's temporary CPT code, yeah.
Okay. Could you comment on the potential price level of INO- 3107, and what, realistically speaking, what market adoption rate could be at that price level?
Yeah. So I think it's still a little early to be talking about pricing. But what I can say is, you know, there's an extremely high unmet medical need. These patients have a real need for a therapeutic alternative to surgery. The RRP Foundation put out some data a few years ago saying that the average annual cost of surgery is about $72,000 per patient. That doesn't include the impact on quality of life and all of the other costs associated with treating the disease. I think what's a good potential analog here is Ogsiveo, which was recently approved for treatment of desmoid tumors last year. Desmoid tumors are benign tumors of connective tissue. Like RRP, they're also rarely fatal.
And like RRP, the current standard of care prior to Ogsiveo, was repeated surgery, which obviously impacts patient's quality of life. So I think, you know, while it's not a perfect analog, there's some good parallels, between RRP and what we're trying to do with INO-3107, which is, really eliminate the need for future surgeries, compared with use of Ogsiveo.
Thank you. Is INO-3107 protected by any issued patents?
It is. So we have a broad patent portfolio. As Mike has mentioned, this is a combination product. So we have the DNA plasmid component as well as the device. We have an issued U.S. patent, just on the plasmid component, which goes out to 2041, and we have device and other patents that go out into the mid-2040s.
Got it. Do you think potential sales from INO-3107 alone could make the company cash flow positive?
It's a great question. What I can say is we do anticipate sales from INO-3107 being able to support development of other candidates within our pipeline, and I think we're gonna have to see how it goes, and we'll be able to say more about that in the future.
Does the company have sufficient capital to fund operations for the next two years?
So our cash runway currently goes out to the third quarter of 2025. As you mentioned, at the end of the last quarter, we had $105 million in cash, and we've since completed a raise of about $33.2 million, after deduction of commissions, et cetera.
Could you just give us a review of the upcoming candidates within the next 12-18 months?
Yeah. So following on behind, INO-3107, we have INO-3112, which is another HPV-related candidate, for treatment of HPV -16 and 18, oropharyngeal squamous cell carcinoma, also known as throat cancer. We're looking to start a phase III trial evaluating INO-3112 in combination with LOQTORZI, which is a PD-1 inhibitor developed by Coherus BioSciences, recently approved for nasopharyngeal carcinoma here in the U.S. We, at our last earnings call, we talked about some feedback that we've had from the FDA, that gives us confidence that we'll be able to move forward with that phase III trial design. Our next steps there are to go and talk to the European regulators about that trial design, because we want to conduct a study across both North America and Europe.
And then following on behind INO-3112, we have INO-4201, which is an Ebola booster vaccine candidate that we recently announced further immunogenicity data for, and also some feedback from the FDA giving us, we think, a path forward for that candidate. And then INO-5401, that we evaluated for newly diagnosed glioblastoma, also being evaluated in BRCA-positive people for the prevention of cancer, and we're excited about that candidate as well. And then finally, we have some early-stage candidates, which we think have really transformative potential. And this is where we're encoding monoclonal antibodies on plasmids.
We're then able to get those monoclonal antibody proteins expressed and functionally assembled within the cells and secreted into the bloodstream, and we'll be hopefully publishing our first data coming out from a phase I clinical trial on that technology later on this year. And we also have some exciting what we call DNA-launched nanoparticle vaccines just going into the clinic as well. And this is where we're able to encode a nanoparticle scaffold, as well as the antigens that are used to decorate the scaffold, all within DNA plasmids, and have those self-assemble within the body and generate strong immune responses.
We're very excited to continue to optimize the key strengths of our platform, the ability to drive these antigen-specific targeted T -cells with lytic potential, the ability to drive strong antibody responses, and the ability to really drive production of proteins within the body from DNA.
That's a very rich pipeline. But, regarding 5401, what are the next steps? When can we see some update from 5401?
Yeah. So for INO-5401, we've just been wrapping up that phase II study in glioblastoma. We're in discussions with our partner, Regeneron, on next steps for that candidate and hope to be saying more about it in future planning calls and conferences.
Great. Thank you. So lastly, what is the key takeaway message, for investors today?
I think the key takeaway message for investors is that INOVIO is looking forward to becoming a commercial-stage company, with filing our first BLA this year and hopefully a potential launch next, next year. And we have a deep pipeline of other candidates following on behind INO-3107. It's an exciting time.
Yeah, it is. Well, best wishes, and thank you for joining us today.
Thank you.